Zhang Zhe, He Qinsi, Fu Si, Zheng Zhi
Department of Chinese Medical Gastrointestinal of China-Japan Friendship Hospital, 2 Yinghua Dongjie, Beijing, 100029, Beijing, People's Republic of China.
Medicl College of Nanchang University, Nanchang, 330029, Jiangxi, People's Republic of China.
Pathol Oncol Res. 2017 Apr;23(2):329-334. doi: 10.1007/s12253-016-0105-2. Epub 2016 Sep 5.
Esophageal cancer is a deadly disease in the esophagus with a poor prognosis. Over 90 % of esophageal cancer is esophageal squamous cell carcinoma (ESCC) and its pathogenic mechanisms remain unclear. Epidemiology study found a strong gender difference with a sex ratio of 8-9:1 in favor of males, but the molecular mechanisms for so striking gender difference are poorly understood so far. In the present study, we demonstrated the expression of estrogen receptors in human ESCC cells. 17β-E2 but not 17α-E2 was found to dose-dependently suppress the cell proliferation of human ESCC cells, which was attenuated by estrogen receptor antagonist ICI1 82,780. Furthermore, 17β -E2 but not 17α-E2 10 nM markedly induced both intracellular Ca release and extracellular Ca entry into ESCC cells, which was again attenuated by estrogen receptor antagonist ICI182,780. Taken together, our data clearly demonstrate that estrogen exerts anti-proliferative action on human ESCC cells likely through estrogen receptor-Ca signaling pathway, which may provide a reasonable explanation on the striking male predominance of ESCC.
食管癌是一种发生于食管的致命性疾病，预后较差。超过90%的食管癌为食管鳞状细胞癌（ESCC），其致病机制尚不清楚。流行病学研究发现，食管癌存在明显的性别差异，男女比例为8 - 9:1，男性占优势，但迄今为止，这种显著性别差异的分子机制仍知之甚少。在本研究中，我们证实了雌激素受体在人ESCC细胞中的表达。发现17β - E2而非17α - E2能剂量依赖性地抑制人ESCC细胞的增殖，雌激素受体拮抗剂ICI182,780可减弱这种抑制作用。此外，17β - E2而非17α - E2（10 nM）能显著诱导ESCC细胞内的钙释放和细胞外钙内流，雌激素受体拮抗剂ICI182,780同样可减弱这种诱导作用。综上所述，我们的数据清楚地表明，雌激素可能通过雌激素受体 - 钙信号通路对人ESCC细胞发挥抗增殖作用，这可能为ESCC显著的男性优势提供了合理的解释。
